The present invention relates to novel substituted tetrahydrobenzothiazoles useful as pharmaceutical agents, to methods for their production, to pharmaceutical compositions which include these compounds and a pharmaceutically acceptable carrier, and to pharmaceutical methods of treatment. More particularly, the novel compounds of the present invention are dopamine agonists having selectivity for the presynaptic dopamine receptor, i.e., an autoreceptor. The advantage of an autoreceptor agonist is that it modulates the activity of dopaminergic systems selectively, without the postsynaptic stimulation which is inherent to nonselective dopamine agonists.
Compounds of Formula A ##STR1## wherein R.sup.1 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, an alkenyl or alkynyl group each having 3 to 6 carbon atoms, an alkanoyl group having 1 to 6 carbon atoms, a phenyl alkyl or phenyl alkanoyl group having 1 to 3 carbon atoms in the alkyl part, whilst the above-mentioned phenyl nuclei may be substituted by 1 or 2 halogen atoms,
R.sup.2 represents a hydrogen atom or an alkyl group with 1 to 4 carbon atoms,
R.sup.3 represents a hydrogen atom, an alkyl group with 1 to 7 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an alkenyl or alkynyl group having 3 to 6 carbon atoms, an alkanoyl group having 1 to 7 carbon atoms, a phenyl alkyl or phenyl alkanoyl group having 1 to 3 carbon atoms in the alkyl part, whilst the phenyl nucleus may be substituted by fluorine, chlorine or bromine atoms,
R.sup.4 represents a hydrogen atom, an alkyl group with 1 to 4 carbon atoms, an alkenyl or alkynyl group having 3 to 6 carbon atoms or
R.sup.3 and R.sup.4 together with the nitrogen atom between them represent a pyrrolidino, piperidino, hexamethyleneimino or morpholino group are disclosed in U.S. Pat. No. 4,731,374 as having pharmacological properties, particularly a hypotensive effect on blood pressure, a heart rate lowering effect, and an effect on the central nervous system, particularly a stimulant effect on the dopamine receptors.
However, the benzothiazoles disclosed in U.S. Pat. No. 4,731,374 do not suggest the combination of structural variations of the compounds of the present invention described hereinafter. Furthermore, the aforementioned thiazole derivatives are not disclosed as dopamine agonists having selectivity for the presynaptic dopamine receptor.